Genetically Encoded Photo-cross-linkers Map the Binding Site of an Allosteric Drug on a G Protein-Coupled Receptor

被引：53

作者：

Grunbeck, Amy ^{[1
]}

Huber, Thomas ^{[1
]}

Abrol, Ravinder ^{[2
]}

Trzaskowski, Bartosz ^{[2
]}

Goddard, William A., III ^{[2
]}

Sakmar, Thomas P. ^{[1
]}

机构：

[1] Rockefeller Univ, Lab Mol Biol & Biochem, New York, NY 10065 USA

[2] CALTECH, Mat & Proc Simulat Ctr MC 139 74, Pasadena, CA 91125 USA

来源：

ACS CHEMICAL BIOLOGY | 2012年 / 7卷 / 06期

关键词：

SMALL-MOLECULE; HIV-1; ENTRY; AMINO-ACID; CCR5; GPCR; MUTAGENESIS; ANTAGONISTS; DISCOVERY; COMPOUND; PEPTIDE;

D O I：

10.1021/cb300059z

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

G protein-coupled receptors (GPCRs) are dynamic membrane proteins that bind extracellular molecules to transduce signals. Although GPCRs represent the largest class of therapeutic targets, only a small percentage of their ligand-binding sites are precisely defined. Here we describe the novel application of targeted photo-cross-linking using unnatural amino acids to obtain structural information about the allosteric binding site of a small molecule drug, the CCR5-targeted HIV-1 co-receptor blocker maraviroc.

引用

页码：967 / 972

页数：6

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